ANHİDRİT İÇEREN KOPOLİMER-İLAÇ TAŞIYICI SİSTEMLERİN TASARIMI, NİTROKSİT ARACILIĞIYLA POLİMERİZASYONU (NMP) VE KARAKTERİZASYONU

Abstract

In recent years developments in the field of material science and bio-technology, feed off each other and the desired functional structure for use in many areas of design, quality of materials, synthesis, characterization and applications of enables cancer caused deregulation of cell growth and normal genes, or a disease caused by diversion of regulatory mechanisms. In developed countries cancer is the second among the most common cause of death after cardiovascular diseases. According to recent statistics, in 2020, there will more than 15 million cancer patients around the world. Most of cancer depending on the type and stage of cancer localization can be treated with applications such as chemotherapy, surgery, and radiation therapy. Nowadays treatment of cancers is possible not only with cytotoxic drugs and biological agents, but also via antibodies. Cancer therapy drug is analog of a fluorinated pyrimidine. 5- fluorouracil (5-FU) with the wide range of usage and is one way the need as well as a single agent administered to the patient intravenously in combination with anticancer drugs. This drug especially is used to treat ovarian cancer, breast, lung, thyroid cancer, soft tissue sarcomas, and particularly for treat certain types of leukemia. 5-FU have undesirable complications such as irregular heartbeats, heart failure. Other side effects are mouth sores, digestive problems, hair loss, hand and foot syndrome. It is possible to increase the activity of 5-FU and eliminate/or minimize side effects with polymer/5-FU conjugation in biological systems. Polymers, metals, nanoparticles, or maybe ceramic materials could be used as drug delivery systems. Acquire various features changing the shape and size of the particles depending on the material used and the method of production. Liposomes, solid lipid particles, micelles, cells, dendrimers, polymer-drug conjugates, hydrogels are systems studied in this regard. Most anticancer drugs have low molecular weight and can easily penetrate through the cell wall. This reduces the half-life of drugs and causes damage to other cells as well as tumor cells. To reduce side effects, increased bioavailability of the drugs and provide specific targeting, various drug delivery and release systems in different sizes are being developed liposomes, solid lipid nanoparticles, polymeric micelles and self-induced polymeric aggregates comprising these micelles. The aim of thesis is to synthesize of poly(MA-alt-NVP) first in different compositions through charge transfer complex (CTC) copolymerization between N-vinyl pirrolidone (NVP) and maleic anhydrid (MA) by complex radical polymerization and nitroxide mediated polymerization (NMP) with is controlled polymerization technique, further steps involve copolymer characterization and chemical conjugation of 5-Florourasil (5-FU) to this functional and water-soluble special copolymer system. The complex formed between MA and NVP was investigated by using UV-Vis spectroscopy. Complex molar absorption coefficient (εAD), Complex equilibrium constant (KAD) and transition energy (EAD) is determined by using Scott equation. Compositions of the synthesized copolymers were determined by elemental analysis method. Reactivity ratios of MA and NVP monomers in the copolymer were calculated by using elemental analysis data and Kelen-Tüdös (KT), Mayo-Lewis (ML), Fineman-Ross (FR) and Inverted Fineman-Ross (IFR) equations. Obtained poly(MA-alt-NVP) and poly(MA-alt-NVP)-5-FU conjugate via charge transfer complex (CTC) polymerization and nitroxide mediated polymerization (NMP) system and structure properties are clarified by using ATR-FTIR, NMR (1H, 13C ve 19F), XRD, Fluorescence, HR-Raman, UV-Vis, DSC, TGA and determination of molecular weight by using MALDI-TOF-MS methods. Biological activity of poly(MA-alt-NVP) and poly(MA-alt-NVP)-5-FU conjugate were investigated via Saos-2 cells by using the dsDNA method to assess the number of viable cells and cell proliferation.